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Association Study of the 5-HTTLPR Polymorphism and Depression in 75-Year-Old Nondemented Subjects From the Vienna Transdanube Aging (VITA) Study

J Clin Psychiatry 2006;67(9):1373-1378

Background: The site of effect for the selective serotonin reuptake inhibitors (SSRIs) is the serotonin transporter (5-HTT), which is extensively investigated for its involvement in depressive symptoms. The 5-HTT gene exhibits a 5'-promoter-based length polymorphism (5-HTTLPR) that affects the transcription efficiency and activity, known as short (S) and long (L) alleles. We studied the association of this polymorphism in old age and depression in the Vienna Transdanube Aging (VITA) study, excluding subjects with dementia.

Method: We used retrospective data from the baseline of the VITA study, which is a cohort study of all inhabitants of a geographical area aged 75 years (N = 544). Depression was diagnosed and classified strictly according to the DSM-IV. To eliminate dementia effects, we excluded subjects with a Clinical Dementia Rating higher than or equal to 1 and/or a Mini-Mental State Examination score lower than 24. Genotyping for the 5-HTTLPR L/S allele was conducted using polymerase chain reaction methodology.

Results: We found significantly higher SS genotype frequency in all subjects with past/present depression compared to controls (trend test, p = .01). The SS genotype frequency was especially high in subjects with onset of depression before age 65. No correlations were found between genotypes/S allele carriers and actual Hamilton Rating Scale for Depression, Short-Geriatric Depression Scale, and anxiety scale scores.

Conclusions: These observations of higher frequency of the 5-HTTLPR S allele in subjects with past/present depression fit with previous findings and point to the important role of 5-HTT in depression.